A Nonionic Polyethylene Oxide (PEO) Surfactant Model: Experimental and Molecular Dynamics Studies of Kolliphor EL |
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Authors: | Estelle J.A. Suys Dallas B. Warren Anna C. Pham Cameron J. Nowell Andrew J. Clulow Hassan Benameur Christopher J.H. Porter Colin W. Pouton David K. Chalmers |
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Affiliation: | 1. Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Victoria 3052, Australia;2. ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Victoria 3052, Australia;3. Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Victoria 3052, Australia;4. Lonza Pharma Sciences, Strasbourg, France;5. Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Victoria 3052, Australia |
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Abstract: | Polyethoxylated, nonionic surfactants are important constituents of many drug formulations, including lipid-based formulations. In an effort to better understand the behavior of formulation excipients at the molecular level, we have developed molecular dynamics (MD) models for the widely used surfactant Kolliphor EL (KOL), a triricinoleate ester of ethoxylated glycerol. In this work, we have developed models based on a single, representative molecular component modeled with 2 force field variations based on the GROMOS 53A6DBW and 2016H66 force field parameters for polyethoxylate chains. To compare the computational models to experimental measurements, we investigated the phase behavior of KOL using nephelometry, dynamic light scattering, cross-polarized microscopy, small-angle X-ray scattering, and cryogenic transmission electron microscopy. The potential for digestion of KOL was also evaluated using an in vitro digestion experiment. We found that the size and spherical morphology of the KOL colloids at low concentrations was reproduced by the MD models as well as the growing interactions between the aggregates to from rod-like structures at high concentrations. We believe that this model reproduces the phase behavior of KOL relevant to drug absorption and that it can be used in whole formulation simulations to accelerate the formulation development. |
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Keywords: | surfactant molecular dynamics phase transition small-angle X-ray scattering dynamic light scattering cryogenic transmission electron microscopy DLS dynamic light scattering PEO polyethylene oxide cryo-TEM cryogenic transmission electron microscopy LBF lipid-based formulation MD molecular dynamics SASA solvent accessible surface area SAXS small-angle X-ray scattering KOL Kolliphor EL PDI polydispersity index GI gastrointestinal |
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